A Very Big Clue to Understanding Dry AMD

Dry AMD with atrophy is still a big cause of vision loss. Vitamin and zinc supplements reduce the rate of vision loss in AMD mainly by decreasing the risk of developing new blood vessels or wet AMD. Non-steroidal anti-inflammatory drugs such as aspirin, ibuprofen, or naproxen may decrease the rate of progression to atrophy by decreasing inflammation but they aren’t a cure all.

There was a very interesting article which is scheduled to be published in the October 2, 2008 issue of the New England Journal of Medicine showing an association of variants in the toll-like receptor 3 gene with decreasing the risk of geographic atrophy in people with AMD. This receptor encodes for a viral sensor that is associated with innate immunity-meaning fighting off viral infections.

The scientists put two genetically different toll-like receptors in mice and then injected double stranded RNA into the vitreous; this is analogous to getting a virus. The variant of the receptor that protected against atrophy in people with AMD protected against cell death of the pigment epithelium in mice compared to the normal variant.

How about in layperson’s terms? The idea is that a virus that contains double stranded RNA infects the retinal pigment epithelium. The toll-like receptors are activated to fight the virus. One genetic variant of the receptor perhaps causes more inflammation causing the death of the retinal pigment epithelial cell compared to the other variant. Once again, too much inflammation might be bad.

So how to you decrease atrophy in dry AMD? You can have the genetic variant of toll-like receptor that protects against atrophy. If you don’t have this variant in your genes, perhaps in the future you’ll be able to get the good variant transplanted into your retina. The hooker with this is that usually genes are transplanted via viruses and viruses might be bad especially if you have AMD. Probably a more realistic route would be to decrease the inflammation in the outer retina. We don’t know how to selectively decrease the inflammation started by the toll-like receptor. For now, I would still take 325 mg of aspirin, 200mg of ibuprofen, or 275mg of Naproxen a day.

We need much more information but this recent study is a very impressive start into understanding a complex disease.

References:

1. Yang, Z, Straaton, C, Francis, PJ, et al. Toll-like Receptor 3 and Geographic Atrophy in Age-Related Macular Degeneration. N Engl J Med. 2008;359(14):1456-1463

(reference updated 10-2-2008)